Combinatorial Influence of Bone Marrow Aspirate Concentrate (BMAC) and Platelet-Rich Plasma (PRP) Treatment on Cutaneous Wound Healing in BALB/c Mice.

Bone marrow, a soft spongy tissue, is containing mesenchymal stem cells, that are well-recognized according to their self-renewability and stemness. Therefore, we hypothesized that bone marrow aspirate concentrate (BMAC) could have a pivotal influence on the process of wound healing in particular when it is combined with platelet-rich plasma (PRP). Thirty-six albino mice (BALB/c) were used in the study and they were grouped as negative-control, PRP treated, BMAC treated and BMAC plus PRP treated. An incisional wound (1 cm2) was made at the back of mouse and their wounds were treated according to their treatment plan and group allocations. Later, the skin at the treated wound sites was collected on days 7, 14, and 21 for histopathological investigation. The results showed that there was a statistically significant difference in BMAC+PRP-treated wounds over the rest of the treated groups in the acceleration of wound healing throughout the experiment by increasing the rate of wound contraction, re-epithelization process, and granulation tissue intensity with fluctuated infiltration in the number of the neutrophils, macrophages, and lymphocytes, also restoration of the epidermal and dermal thickness with less scarring and hair follicle regeneration vs to the negative-control, PRP and BMAC only treated groups. Our findings indicated that BMAC containing mesenchymal stem cells is an efficient approach, which can be used to enhance a smooth and physiopathological healing process, especially when it is used in combination with PRP.

Vitamin D receptor gene polymorphism and serum vitamin D level as risk factors for acquiring Type II diabetes mellitus.

The studies on the relationship between type 2 diabetes mellitus (T2DM) risk and vitamin D receptor (VDR) gene polymorphisms are still inconclusive. Therefore, the objective of the study was to assess possible risks of acquiring T2DM due to polymorphisms in the VDR gene or abnormal serum levels of VD. 362 participants (181 T2DM patients and 181 healthy controls) from the Diabetic Center, Sulaimaniyah/Iraq, from December 2020 to May 2021 were volumtarily enrolled in the study. For each participant, HbA1c, fasting blood sugar (FBS), serum cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), markers of calcium homeostasis, alkaline phosphatase (ALP), phosphorus, VD and insulin were measured. In addition, FokI, TaqI, ApaI, and BsmI genotypes were also performed using Polymerase Chain Reaction (PCR). The results showed that VD level was significantly lower in T2DM compared to the control group. While, HbA1c was significantly higher in T2DM than in the control group. In contrast to  AA (P=0.034) and CC (P=0.011) genotype of ApaI (rs7975232) gene polymorphism, which were dominant among the control group, AC-genotype was significantly (P=0.0001) dominat among T2DM group. Meanwhile, TT-genotype of TaqI (rs731236) was  significantly (P=0.05) dominant among control group. While there were not any significant differences between other genotypes among T2DM and control groups. In conclusion, low VD-level is a possible risk factor for developing T2DM, and an association was found, especially between ApaI genotypes and T2DM.

Expression of Epsin3 and its interaction with Notch signalling in oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice. In this study, we have investigated the role of Epsin3, an endocytic adaptor protein, and Notch1, a transmembrane signalling protein, in oral carcinogenesis with a view to explore their potential as biomarkers. METHODS: Oral cancer cell lines and a normal oral keratinocyte cell line were used together with tissue samples of normal oral mucosa (n = 21), oral epithelial dysplasia (n = 74) and early stage (Stages I and II) oral squamous cell carcinoma (n = 31). Immunocytochemical staining, immunoblotting and real-time quantitative polymerase chain reaction (PCR) were performed to assess protein as well as gene expression levels. RESULTS: The expression levels of Epsin3 and Notch1 mRNA and protein are variable across different oral squamous cell carcinoma derived cell lines. Epsin3 was upregulated in oral epithelial dysplasia and oral squamous cell carcinoma tissues compared with normal epithelium. Overexpression of Epsin3 resulted in a significant reduction of Notch1 expression in oral squamous cell carcinoma. Notch1 was generally downregulated in the dysplasia and oral squamous cell carcinoma samples. CONCLUSION: Epsin3 is upregulated in oral epithelial dysplasia and oral squamous cell carcinoma and has the potential to be used as a biomarker for oral epithelial dysplasia. Notch signalling is downregulated in oral squamous cell carcinoma, possibly through an Epsin3-induced de-activation pathway.

Synthesis and in vivo evaluation of three fluid spray dried hybrid ciprofloxacin microparticles in Sprague Dawley rats.

The aim of this study is to prepare and characterise mucoadhesive silica-coated silver nanoparticles loaded with ciprofloxacin (S-AgNPs-CSCFX), and investigate serum biochemical, haematological, and histopathological effects in Sprague Dawley rats upon oral administration. S-AgNPs-CSCFX microparticles were prepared using three fluid nozzle spray drying and characterised by scanning electron microscopy (SEM), X-ray dispersive spectrometry (EDX), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), zeta potential and particles size measurements and X-ray powder diffraction (XRPD). Adult male Sprague Dawley rats were randomly divided between six-treated groups, including blank S-AgNPs and S-AgNPs-CSCFX (LD: Low dose; MD: Median Dose; HD: High Dose) and control group. Each group was treated daily to evaluate the effect of the prepared particles on the lipid profile, serum biochemical, hormonal level, haemogram, and vital organ histopathology. The results showed successful encapsulation of silver nanoparticles which resulted in spherical-shaped S-AgNPs-CSCFX with an average size of 1-5 µm and surface charge of 25.2 ± 5.52 mv. The in-vivo results showed that different doses of blank S-AgNPs and S-AgNPs-CSCFX had no significant toxic effects on the physiological, biochemical, and haematological parameters. There were no marked histopathological alterations in the vital organs of the treated rats with blank and loaded particles.

Antileukemic Effect of Palladium Nanoparticles Mediated by White Tea (Camellia sinensis) Extract In Vitro and in WEHI-3B-Induced Leukemia In Vivo.

This study investigated the in vivo antileukemic activity of palladium nanoparticles (Pd@W.tea-NPs) mediated by white tea extract in a murine model. The cell viability effect of Pd@W.tea-NPs, "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of Pd@W.tea-NPs in WEHI-3B cells were evaluated. The effects of Pd@W.tea-NPs administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. Pd@W.tea-NPs reduced the viability of WHEI-3B cells with IC50 7.55 µg/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. Pd@W.tea-NPs increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by Pd@W.tea-NPs with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. Pd@W.tea-NPs afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.

Metabolic programming of a beige adipocyte phenotype by genistein.

SCOPE: Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. METHODS AND RESULTS: We observed that application of genistein to 3T3-L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin, and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD-137 and UCP1). Transcripts with a role in adipocyte differentiation (Cebpß, Pgc1α, Sirt1) peaked at different times after application of genistein. These responses were not affected by the estrogen receptor (ER) antagonist fulvestrant, revealing that this action of genistein is not through the classical ER pathway. The Sirt1 inhibitor Ex-527 curtailed the genistein-mediated increase in UCP1 and Cebpß mRNA, revealing a role for Sirt1 in mediating the effect. Baseline oxygen consumption and the proportional contribution of proton leak to maximal respiratory capacity was greater for cells exposed to genistein, demonstrating greater mitochondrial uncoupling. CONCLUSIONS: We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease.